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Comparative genomics of sugar-eating bats: Implications for the genetics of glucose metabolism and diabetes

Periodic Reporting for period 1 - CHIROGLU (Comparative genomics of sugar-eating bats: Implications for the genetics of glucose metabolism and diabetes)

Berichtszeitraum: 2017-06-01 bis 2019-05-31

Genetic adaptation of bats to sugar-rich diet

Diabetes and impaired glucose tolerance are major threats to human health, affecting more than 400 million individuals, and costing billions to society. These conditions are often linked to poor diet, notably an excessive consumption of sugar, combined with a lack of physical activity. In addition, mounting evidence suggests they also have major genetic components. To date, our understanding of the genetics of sugar metabolism has been greatly informed by studies of humans and laboratory organisms. Yet powerful insights may also be obtained by studying non-model species that show evolutionary adaptations for high sugar diets.

Among mammals, bats are unique in their dietary specialisations, with up to eight lineages having independently evolved nectar-feeding. How these bats are able to survive on high sugar diets, and regulate their blood sugar to resist the damaging effects of glucose toxicity, is not known. With the rapid advances in DNA sequencing technology, we are now able to gain a deeper understanding of what makes a species unique and how its genetic make-up matches the challenge imposed by the environmental conditions such as diet. This project set out to discover the candidate genes under selection in lineages of nectar-feeding bats, which may allow these species to subsist on high-sugar diets without developing metabolic diseases such as diabetes.
The EU-funded CHIROGLU (Comparative genomics of sugar-eating bats:
Implications for the genetics of glucose metabolism and diabetes) set out to gain an improved understanding of the evolution of nectarivory in Old World bats. To this end, we aimed to reconstruct the most complete phylogeny of Old World fruit bats to date, and then use this phylogeny to address several questions concerning genetic adaptations to extreme sugar-rich diets.

For this project, tissue samples of 144 fruit bats species were obtained from specimens preserved in museum collections around the world. Genomic DNA of each species was isolated and used to target ~1500 loci using bait-based sequence capture. These sequences were aligned and used for phylogenetic reconstruction in order to identify the exact number of independent origins of nectarivory within the family. Then, for each locus, we performed tests of positive selection along each of the seven branches that corresponded to independent origins of nectar-feeding.
These results led to the identification of numerous interesting genetic adaptations for sugar-rich diet in bats, with genes under selection found to have key roles in carbohydrate metabolism. Additionally, the project resolved the relationships among Old Word fruit bats, and revealed unexpected paraphyly in a major genus, implying that a taxonomic revision is required. The findings will improve our understanding of how natural selection has driven dietary specialisation in mammals, and will potentially open up new avenues for future studies of sugar metabolic diseases.
Old World fruit bats